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Evaluation of Mutagenic and Genotoxic Activities of Lobeline and Its Modulation on Genomic Instability Induced by Ethanol

Evaluation of Mutagenic and Genotoxic Activities of Lobeline and Its Modulation on Genomic Instability Induced by Ethanol

Liana Dantas da Costa E Silva, Laise Carla Lima Verde Rodrigues, Viviane Ramos Dos Santos, Mariangela da Costa Allgayer, Alexandre de Barros Falcão Ferraz, Helena Campos Rolla, Patrícia Pereira, Jaqueline Nascimento Picada

Life Sci. 2014 May 17;103(2):73-8.

PMID: 24727238

Abstract:

Aim:
Lobeline is a natural alkaloid derived from Lobelia inflata that has been investigated as a clinical candidate for the treatment of alcoholism. In a pre-clinical trial, lobeline decreased the preference for and consumption of ethanol, due to the modulation of the nicotinic acetylcholine receptor. However, the interaction between lobeline and ethanol is poorly known and thus there are safety concerns. The present study was conducted to evaluate the mutagenic and genotoxic effects of lobeline and assess its modulation of ethanol-induced toxicological effects.
Main methods:
CF-1 male mice were divided into five groups. Groups received an intraperitoneal injection of saline solution, lobeline (5 or 10mg/kg), ethanol (2.5 g/kg), or lobeline plus ethanol, once a day for three consecutive days. Genotoxicity was evaluated in peripheral blood using the alkaline comet assay. The mutagenicity was evaluated using both Salmonella/microsome assay in TA1535, TA97a, TA98, TA100, and TA102 Salmonella typhimurium strains and the micronucleus test in bone marrow. Possible liver and kidney injuries were evaluated using biochemical analysis.
Key findings:
Lobeline did not show genotoxic or mutagenic effects and did not increase the ethanol-induced genotoxic effects in blood. Lobeline also protected blood cells against oxidative damage induced by hydrogen peroxide. Biochemical parameters were not altered, indicating no liver or kidney injuries or alterations in lipid and carbohydrate metabolisms.
Significance:
These findings suggest that lobeline does not induce gene or chromosomal mutations, and that this lack of genetic toxicity is maintained in the presence of ethanol, providing further evidence of the safety of this drug to treat alcohol dependence.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP134634	(−)-Lobeline hydrochloride		134-63-4	Price

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